The long-term objective of the Comparative Medicine Research Center in the Department of Veterinary pathology at University of Missouri-Columbia is to enhance advances in biomedical research and thereby improve the human condition by improving the quality and definition of laboratory animals through basic and applied biomedical research related to laboratory animal medicine, pathology, and science. Historically, progress in biomedical research has involved animals. Animals are used in about half of all research funded by the NIH. By improving our understanding of the biology, pathophysiology, diseases, and research uses of the animal 'reagent' more meaningful extrapolation of animal derived data to human health and disease will be possible. Our specific aims include: 1) focused investigations to provide understanding and possible solutions to major contemporary problems affecting the use of animals in research; 2) dissemination of this information through appropriate publications and presentations; and 3) to assist in the application of our research findings. Another aim is to provide research training opportunities and to encourage education in the broad area of laboratory animal science. We have identified six major problems that affect the use of animals in research and in this proposal we present designs of research projects for their study under the following project titles: -- Rodent Orphan Pathoviruses: Molecular Characterization and Development of Diagnostic Reagents -- Rodent Orphan Pathoviruses: Pathogenesis and Interface with Research -- The biology of the Intestinal, Segmented, Filamentous Bacteria of Rodents -- Production of Specific Viral Antigens for Use as Diagnostic Reagents Using a Baculovirus Expression System -- Viral Gene Amplification Assays of detection of Murine Viruses in Biological Samples --Pathogenesis of Cilia-Associated Respiratory Bacillus Infection